Circadian Rhythm Disruption May Be “Important Prodromal Feature” for PD

Reduced circadian rhythmicity may be associated with an increased risk of Parkinson disease (PD) among elderly individuals, according to new findings published in JAMA Neurology.

“Circadian rhythm disruption in elderly individuals may represent an important prodromal feature for Parkinson disease, and future studies should test whether circadian disruption could also be a risk factor for Parkinson disease and whether strategies to improve circadian function affect the risk of Parkinson disease,” the authors of the study wrote.

These findings emerged from an ancillary sleep study of the longitudinal cohort Osteoporotic Fractures in Men Study (MrOS), which was performed from December 1, 2003, to March 31, 2005. A total of 2930 men (mean age 76.3 years) without PD at baseline were included in the present analysis. The researchers analyzed data from February 1, 2019, through August 31, 2019.

Exposures were 24-hour rest-activity rhythm (RAR) parameters, including mesor, amplitude, acrophase, and robustness, which were generated via wrist actigraphy-extended cosinor analysis. The main outcome of the study was defined as incident PD diagnosed by a physician. The association of RAR parameter quartiles and incident PD risk was examined using multivariable logistic regression.

The results of the study indicated that 78 (2.7%) of 2930 men developed PD over a follow-up period of 11 years. Following adjustment for all covariates, PD risk was found to increase with the following:

• Decreasing circadian amplitude (odds ratio [OR] per 1-SD decrease 1.77)
• Decreasing mesor (OR per 1-SD decrease 1.64)
• Decreasing robustness (OR per 1-SD decrease 1.54)

Notably, the risk of developing PD was approximately 3 times higher among men in the lower quartile of amplitude, mesor, and robustness compared with men in the highest quartile of amplitude (OR 3.11), mesor (OR 3.04), and robustness (OR 2.64). This association remained significant following adjustment for nighttime sleep disturbances and duration in the lowest quartile compared with the highest quartile (OR for amplitude 3.56; OR for mesor 3.24; OR for robustness 3.34).

The above associations were somewhat mitigated, but the pattern stayed similar following exclusion of cases of PD that developed within 2 years after baseline in the lowest quartile compared with the highest quartile (OR for amplitude 2.40; OR for mesor 2.76; OR for robustness 2.33). The researchers did not observe any significant association between acrophase and PD risk.

—Christina Vogt

Reference:
Leng Y, Blackwell T, Cawthon PM, Ancoli-Israel S, Stone KL, Yaffe K. Association of circadian abnormalities in older adults with an increased risk of developing Parkinson disease. JAMA Neurol. Published online June 15, 2020. doi:10.1001/jamaneurol.2020.1623